Osteoporosis is a major medical problem affecting over 44 million individuals in the US, and a substantial number of those individuals will experience a low impact fracture. To effectively assess fracture risk in this population, one must be able to directly measure bone quality parameters in a patient that reflects the overall mechanical competence of the bone tissue. No current method or instrument can safely and practically perform that task. The BioDent Reference Point Indenter has been the subject of laboratory research for over six years, and recent studies support its ability to measure critical bone properties in osteoporotic individuals. BioDent quantifies bone tissue microfractures through the use of a microindentation process, and there is a strong relationship between microfracture and general fracture incidence. The central hypotheses of this proposal are (HP 1) minimally invasive micro-level in situ bone quality measurements via Reference Point Indentation are robust indicators of organ-level bone fragility; (HP 2) Reference Point Indentation measurements made at the tibiae exhibit similar trends of fragility as the common fracture sites within the same donor; and (HP 3) Reference Point Indentation measurements can further discriminate bone fragility with higher fidelity and accuracy than BMD. The proposed study will rigorously test these hypothesis using the BioDent Reference Point Indentation system, mechanical testing, and DeXA to demonstrate that minimally invasive indentations can predict bone fragility to a greater degree of accuracy than DeXA. PUBLIC HEALTH RELEVANCE: There are over 44 million osteoporosis patients in the US. Currently, no diagnostic method can predict the high number of low impact fractures observed among those individuals. The proposed study is directed to an instrument that safely and directly measures the resistance of bone material to fracture.